Cones Respond to Light in the Absence of Transducin β Subunit

Mammalian cones respond to light by closing a cGMP-gated channel via a cascade that includes a heterotrimeric G-protein, cone transducin, comprising G alpha t2, G beta 3 and G gamma t2 subunits. The function of G beta gamma in this cascade has not been examined. Here, we investigate the role of G beta 3 by assessing cone structure and function in G beta 3-null mouse (Gnb3(-/-)). We found that G beta 3 is required for the normal expression of its partners, because in the Gnb3(-/-) cone outer segments, the levels of G alpha t2 and G gamma t2 are reduced by fourfold to sixfold, whereas other components of the cascade remain unaltered. Surprisingly, Gnb3(-/-) cones produce stable responses with normal kinetics and saturating response amplitudes similar to that of the wild-type, suggesting that cone phototransduction can function efficiently without a G beta subunit. However, light sensitivity was reduced by approximately fourfold in the knock-out cones. Because the reduction in sensitivity was similar in magnitude to the reduction in G alpha t2 level in the cone outer segment, we conclude that activation of G alpha t2 in Gnb3(-/-) cones proceeds at a rate approximately proportional to its outer segment concentration, and that activation of phosphodiesterase and downstream cascade components is normal. These results suggest that the main role of G beta 3 in cones is to establish optimal levels of transducin heteromer in the outer segment, thereby indirectly contributing to robust response properties.